tbuckley/cabot-search huggingface dataset:
Case 7-2023: A 70-Year-Old Man with Covid-19, Respiratory Failure, and Rashes
Authors: Michael K. Mansour, Joseph D. King, Steven T. Chen, Jay A. Fishman, Rosalynn M. Nazarian
Journal: New England Journal of Medicine (2023)

Pr esentation of C a seDr. Carolina Geadas (Medicine): A 70-year-old man with a history of kidney transplantation was evaluated at this hospital because of multiple erythematous rashes that had developed during an admission for respiratory failure, pneumococcal bacteremia, and kidney failure.Approximately 4.5 years before the current admission, the patient received a diagnosis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis after he presented with progressive glomerulonephritis with kidney failure and new hemoptysis.The anti-myeloperoxidase antibody titer was 221.0 U (reference value, <2.8).The patient underwent plasmapheresis, and cyclophosphamide and prednisone were administered.Hemodialysis was initiated.Two weeks later, rituximab was administered, and cyclophosphamide and prednisone were discontinued.During the next 4 years, his renal function did not improve, and treatment with rituximab and hemodialysis was continued.Four months before the current admission, the patient underwent transplantation of a kidney from a deceased donor with hepatitis C virus antibody-positive status.After the kidney transplantation, immunosuppressive therapy included a dose of basiliximab, mycophenolate mofetil, tacrolimus, and tapering doses of prednisone.The patient had delayed graft function; the blood creatinine level decreased from approximately 4.00 mg per deciliter (354 mmol per liter) immediately after transplantation to 1.50 mg per deciliter (133 mmol per liter) 6 weeks later.Six days before the current admission, at a routine follow-up visit, the creatinine level was 1.33 mg per deciliter (118 mmol per liter).Four days before the current admission, the patient began to have central abdominal discomfort, nausea, anorexia, chills, and diarrhea with loose stools three times per day.During the next several days, he noticed decreased urine output and malaise, and he began to have rhinorrhea, cough, sinus congestion, and dyspnea.He was brought to the emergency department of this hospital.
Alveolar Hemorrhage in Idiopathic Multicentric Castleman’s Disease
Authors: Lingtong Huang, Xia Zheng, Xiaohan Huang, Lijun Wang, Xueling Fang, Guojun He, Meng Tang, Huixian Shi, Hongliu Cai
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Alveolar Hemorrhage in Idiopathic Multicentric Castleman's Disease." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp. –
Timing of Antidepressant Discontinuation During Pregnancy and Postpartum Psychiatric Outcomes in Denmark and Norway
Authors: Nhung T. H. Trinh, Trine Munk-Olsen, Naomi R. Wray, Veerle Bergink, Hedvig M. E. Nordeng, Angela Lupattelli, Xiaoqin Liu
Journal: JAMA Psychiatry (2023)

Approximately one-half of women treated for affective disorders discontinue antidepressant use during pregnancy, yet this discontinuation could lead to relapse post partum.To investigate the associations between longitudinal antidepressant fill trajectories during pregnancy and postpartum psychiatric outcomes.This cohort study used nationwide registers in Denmark and Norway. The sample included 41 475 live-born singleton pregnancies in Denmark (1997-2016) and 16 459 in Norway (2009-2018) for women who filled at least 1 antidepressant prescription within 6 months before pregnancy.Antidepressant prescription fills were obtained from the prescription registers. Antidepressant treatment during pregnancy was modeled using the k-means longitudinal method.Initiation of psycholeptics, psychiatric emergencies, or records of self-harm within 1 year post partum. Between April 1 and October 30, 2022, hazard ratios (HRs) for each psychiatric outcome were estimated using Cox proportional hazards regression models. Inverse probability of treatment weighting was used to control for confounding. Country-specific HRs were pooled using random-effects meta-analytic models.Among 57 934 pregnancies (mean [SD] maternal age, 30.7 [5.3] years in Denmark and 29.9 [5.5] years in Norway), 4 antidepressant fill trajectories were identified: early discontinuers (31.3% and 30.4% of the included pregnancies in Denmark and Norway, respectively), late discontinuers (previously stable users) (21.5% and 27.8%), late discontinuers (short-term users) (15.9% and 18.4%), and continuers (31.3% and 23.4%). Early discontinuers and late discontinuers (short-term users) had a lower probability of initiating psycholeptics and having postpartum psychiatric emergencies vs continuers. A moderately increased probability of initiation of psycholeptics was found among late discontinuers (previously stable users) vs continuers (HR, 1.13; 95% CI, 1.03-1.24). This increase in late discontinuers (previously stable users) was more pronounced among women with previous affective disorders (HR, 1.28; 95% CI, 1.12-1.46). No association between antidepressant fill trajectories and postpartum self-harm risk was found.Based on pooled data from Denmark and Norway, a moderately elevated probability of initiation of psycholeptics in late discontinuers (previously stable users) vs continuers was found. These findings suggest that women with severe mental illness who are currently on stable treatment may benefit from continuing antidepressant treatment and personalized treatment counseling during pregnancy.
Nuclear Factor-κB Keeps Basal Cells Undifferentiated in Congenital Diaphragmatic Hernia
Authors: Brian M. Varisco
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"NFκB Keeps Basal Cells Undifferentiated in Congenital Diaphragmatic Hernia." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp. –
Preclinical Efficacy of the Antibody–Drug Conjugate CLDN6–23-ADC for the Treatment of CLDN6-Positive Solid Tumors
Authors: Martina S.J. McDermott, Neil A. O'Brien, Benjamin Hoffstrom, KeWei Gong, Ming Lu, Jun Zhang, Tong Luo, Min Liang, Weiping Jia, Jenny J. Hong, Kevin Chau, Simon Davenport, Bin Xie, Michael F. Press, Richard Panayiotou, Abram Handly-Santana, Joan S. Brugge, Leonard Presta, John Glaspy, Dennis J. Slamon
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Claudin-6 (CLDN6) is expressed at elevated levels in multiple human cancers including ovarian and endometrial malignancies, with little or no detectable expression in normal adult tissue. This expression profile makes CLDN6 an ideal target for development of a potential therapeutic antibody–drug conjugate (ADC). This study describes the generation and preclinical characterization of CLDN6–23-ADC, an ADC consisting of a humanized anti-CLDN6 monoclonal antibody coupled to monomethyl auristatin E (MMAE) via a cleavable linker. Experimental Design: A fully humanized anti-CLDN6 antibody was conjugated to MMAE resulting in the potential therapeutic ADC, CLDN6–23-ADC. The antitumor efficacy of CLDN6–23-ADC was assessed for antitumor efficacy in CLDN6-positive (CLDN6+) and -negative (CLDN6−) xenografts and patient-derived xenograft (PDX) models of human cancers. Results: CLDN6–23-ADC selectively binds to CLDN6, versus other CLDN family members, inhibits the proliferation of CLDN6+ cancer cells in vitro, and is rapidly internalized in CLDN6+ cells. Robust tumor regressions were observed in multiple CLDN6+ xenograft models and tumor inhibition led to markedly enhanced survival of CLDN6+ PDX tumors following treatment with CLDN6–23-ADC. IHC assessment of cancer tissue microarrays demonstrate elevated levels of CLDN6 in 29% of ovarian epithelial carcinomas. Approximately 45% of high-grade serous ovarian carcinomas and 11% of endometrial carcinomas are positive for the target. Conclusions: We report the development of a novel ADC, CLDN6–23-ADC, that selectively targets CLDN6, a potential onco-fetal-antigen which is highly expressed in ovarian and endometrial cancers. CLDN6–23-ADC exhibits robust tumor regressions in mouse models of human ovarian and endometrial cancers and is currently undergoing phase I study.
Efficacy of Methotrexate Alone vs Methotrexate Plus Low-Dose Prednisone in Patients With Alopecia Areata Totalis or Universalis
Authors: Pascal Joly, Audrey Lafon, Estelle Houivet, Nathalie Donnadieu, Marie-Aleth Richard, Alain Dupuy, Emmanuel Delaporte, Philippe Bernard, Laurent Machet, Antonella Tosti, Veronique Del Marmol, Ramon Grimalt, Pierre A. de Viragh, Jacques Benichou, Olivier Chosidow, Philippe Assouly, Pascal Reygagne
Journal: JAMA Dermatology (2023)

Poor therapeutic results have been reported in patients with alopecia areata totalis (AT) or universalis (AU), the most severe and disabling types of alopecia areata (AA). Methotrexate, an inexpensive treatment, might be effective in AU and AT.
Does Past Performance Predict Future Success?—Why This Matters for Measuring Competency
Authors: Stefanie Soelling, Max Riley, Douglas S. Smink
Journal: JAMA Surgery (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Extranodal natural killer/T‐cell lymphoma nasal type in a western population: Molecular profiling identifies new therapeutic targets
Authors: Eva Gonzalez Barca, Laura Tomás‐Roca, Anna Esteve, Marta Rodriguez, Lucía Gato, Ruth Alonso‐Alonso, Alejandro Martin Garcia‐Sancho, Raul Cordoba, Anna Monter‐Rovira, Mariana Bastos‐Oreiro, Juan Miguel Bergua Burgues, Maria Jose Sayas, Maria Cruz Viguria Alegria, Jose Javier Sanchez‐Blanco, Monica Roig Pellicer, Hugo Daniel Luzardo Henriquez, Raquel de Oña, Maria Elena Cabezudo, Maria Stefania Infante, José Antonio Queizán Hernández, Rebeca Sanz‐Pamplona, Oscar Blanco, Ana Mozos, Fina Climent, Miguel Angel Piris
Journal: American Journal of Hematology (2023)

(A) Correlation matrix of unsupervised co-regulated genes, based on the 208 genes included in the NanoString platform. Some of the clusters of co-regulated genes corresponded to the following: Inflammatory cells; Epstein-Barr virus; B-cells; Cytotoxic T-cells; T-cells; and Proliferation. (B) Analysis of genomic alterations by targeted sequencing. Distribution of mutations in the 62 analyzed genes. Rows correspond to sequenced genes, columns represent individual patients. Color coding: green, missense; blue, synonymous; pink, frameshift; violet, Indel; red, stop gained; yellow, UTR.
Racism and Social Determinants of Psychosis
Authors: Deidre M. Anglin
Journal: Annual Review of Clinical Psychology (2023)

The Centers for Disease Control and Prevention has identified racism as a serious threat to public health. Structural racism is a fundamental cause of inequity within interconnected institutions and the social environments in which we live and develop. This review illustrates how these ethnoracial inequities impact risk for the extended psychosis phenotype. Black and Latinx populations are more likely than White populations to report psychotic experiences in the United States due to social determining factors such as racial discrimination, food insecurity, and police violence. Unless we dismantle these discriminatory structures, the chronic stress and biological consequences of this race-based stress and trauma will impact the next generation's risk for psychosis directly, and indirectly through Black and Latina pregnant mothers. Multidisciplinary early psychosis interventions show promise in improving prognosis, but coordinated care and other treatments still need to be more accessible and address the racism-specific adversities many Black and Latinx people face in their neighborhoods and social environments.
GET FIT: A Randomized Clinical Trial of Tai Ji Quan Versus Strength Training for Fall Prevention After Chemotherapy in Older, Postmenopausal Women Cancer Survivors
Authors: Kerri M. Winters-Stone, Fay Horak, Nathan F. Dieckmann, Shiuh-Wen Luoh, Elizabeth Eckstrom, Sydnee A. Stoyles, Eric J. Roeland, Fuzhong Li
Journal: Journal of Clinical Oncology (2023)

PURPOSE To compare the efficacy of tai ji quan versus strength training to prevent falls after chemotherapy in older, postmenopaual women. METHODS We conducted a three-arm, single-blind, randomized controlled trial where older (50+ years), postmenopausal women cancer survivors participated in one of three supervised group exercise programs (tai ji quan, strength training, or stretching control) twice weekly for 6 months and were followed up 6 months after training stopped. The primary outcome was the incidence of falls. Secondary outcomes included fall-related injuries, leg strength (1 repetition maximum; kg), and balance (sensory organization [equilibrium score] and limits of stability [LOS; %] tests). RESULTS Four hundred sixty-two women were enrolled (mean age, 62 ± 6.3 years). Retention was 93%, and adherence averaged 72.9%. In primary analysis, there was no difference in the incidence of falls between groups after 6 months of training, nor during 6-month follow-up. A post hoc analysis detected a significantly reduced incidence of fall-related injuries within the tai ji quan group over the first 6 months, dropping from 4.3 falls per 100 person-months (95% CI, 2.9 to 5.6) at baseline to 2.4 falls per person-months (95% CI, 1.2 to 3.5). No significant changes occurred during 6-month follow-up. Over the intervention period, leg strength significantly improved in the strength group and balance (LOS) improved in the tai ji quan group, compared with controls ( P &lt; .05). CONCLUSION We found no significant reduction in falls for tai ji quan or strength training relative to stretching control in postmenopausal women treated with chemotherapy.
Epitranscriptional Regulation: From the Perspectives of Cardiovascular Bioengineering
Authors: Zhen Bouman Chen, Ming He, Julie Yi-Shuan Li, John Y.-J. Shyy, Shu Chien
Journal: Annual Review of Biomedical Engineering (2023)

The central dogma of gene expression involves DNA transcription to RNA and RNA translation into protein. As key intermediaries and modifiers, RNAs undergo various forms of modifications such as methylation, pseudouridylation, deamination, and hydroxylation. These modifications, termed epitranscriptional regulations, lead to functional changes in RNAs. Recent studies have demonstrated crucial roles for RNA modifications in gene translation, DNA damage response, and cell fate regulation. Epitranscriptional modifications play an essential role in development, mechanosensing, atherogenesis, and regeneration in the cardiovascular (CV) system, and their elucidation is critically important to understanding the molecular mechanisms underlying CV physiology and pathophysiology. This review aims at providing biomedical engineers with an overview of the epitranscriptome landscape, related key concepts, recent findings in epitranscriptional regulations, and tools for epitranscriptome analysis. The potential applications of this important field in biomedical engineering research are discussed.
Cytoplasmic isoleucyl tRNA synthetase as an attractive multistage antimalarial drug target
Authors: Eva S. Istvan, Francisco Guerra, Matthew Abraham, Kuo-Sen Huang, Frances Rocamora, Haoshuang Zhao, Lan Xu, Charisse Pasaje, Krittikorn Kumpornsin, Madeline R. Luth, Haissi Cui, Tuo Yang, Sara Palomo Diaz, Maria G. Gomez-Lorenzo, Tarrick Qahash, Nimisha Mittal, Sabine Ottilie, Jacquin Niles, Marcus C. S. Lee, Manuel Llinas, Nobutaka Kato, John Okombo, David A. Fidock, Paul Schimmel, Francisco Javier Gamo, Daniel E. Goldberg, Elizabeth A. Winzeler
Journal: Science Translational Medicine (2023)

Development of antimalarial compounds into clinical candidates remains costly and arduous without detailed knowledge of the target. As resistance increases and treatment options at various stages of disease are limited, it is critical to identify multistage drug targets that are readily interrogated in biochemical assays. Whole-genome sequencing of 18 parasite clones evolved using thienopyrimidine compounds with submicromolar, rapid-killing, pan-life cycle antiparasitic activity showed that all had acquired mutations in the P. falciparum cytoplasmic isoleucyl tRNA synthetase (cIRS). Engineering two of the mutations into drug-naïve parasites recapitulated the resistance phenotype, and parasites with conditional knockdowns of cIRS became hypersensitive to two thienopyrimidines. Purified recombinant P. vivax cIRS inhibition, cross-resistance, and biochemical assays indicated a noncompetitive, allosteric binding site that is distinct from that of known cIRS inhibitors mupirocin and reveromycin A. Our data show that Plasmodium cIRS is an important chemically and genetically validated target for next-generation medicines for malaria.
Right Ventricular Reverse Remodeling Following Mitral Valve Transcatheter Edge-to-Edge Repair
Authors: Lukas Stolz, Ludwig T. Weckbach, Philipp M. Doldi, Thomas J. Stocker, Felicitas Trimborn, Mathias Orban, Michael Näbauer, Steffen Massberg, Paul Grayburn, Jörg Hausleiter
Journal: JACC. Cardiovascular imaging (2023)
Dyssynchrony and Response to Cardiac Resynchronization Therapy in Heart Failure Patients With Unfavorable Electrical Characteristics
Authors: Jeremy Layec, Marie Decroocq, Francois Delelis, Ludovic Appert, Yves Guyomar, Clémence Riolet, Hélène Dumortier, Amandine Mailliet, Christophe Tribouilloy, Sylvestre Maréchaux, Aymeric Menet
Journal: JACC. Cardiovascular imaging (2023)
Relation of Left Ventricular Diastolic Function to Global Fibrosis Burden
Authors: David Lewandowski, Eric Y. Yang, Duc T. Nguyen, Mohammad A. Khan, Maan Malahfji, Carlos El Tallawi, Mohammed A. Chamsi Pasha, Edward A. Graviss, Dipan J. Shah, Sherif F. Nagueh
Journal: JACC. Cardiovascular imaging (2023)
Left Atrial Strain Is an Independent Predictor of New-Onset Atrial Fibrillation in Dilated Cardiomyopathy
Authors: Anne G. Raafs, Jacqueline L. Vos, Michiel T.H.M. Henkens, Job A.J. Verdonschot, Maurits Sikking, Sophie Stroeks, Suzanne Gerretsen, Mark R. Hazebroek, Christian Knackstedt, Robin Nijveldt, Stephane R.B. Heymans
Journal: JACC. Cardiovascular imaging (2023)
Discordance vs Pressure Recovery in Aortic Stenosis and Post-TAVR
Authors: Luai Madanat, Jason Schott, Ramy Mando, Francis Shannon, Houman Khalili, Josep Rodes-Cabau, David Wood, Janarthanan Sathananthan, Philippe Pibarot, Amr E. Abbas
Journal: JACC. Cardiovascular imaging (2023)
Immature natural killer cells promote progression of triple-negative breast cancer
Authors: Gatha Thacker, Samantha Henry, Ajeya Nandi, Rahul Debnath, Snahlata Singh, Anupma Nayak, Barbara Susnik, Melinda M Boone, Qing Zhang, Susan B Kesmodel, Sanjeev Gumber, Gokul M Das, Taku Kambayashi, Camila O. Dos Santos, Rumela Chakrabarti
Journal: Science Translational Medicine (2023)

Natural killer (NK) cells are cytotoxic lymphocytes that accumulate within the tumor microenvironment and are generally considered to be antitumorigenic. Using single-cell RNA sequencing and functional analysis of multiple triple-negative breast cancer (TNBC) and basal tumor samples, we observed a unique subcluster of Socs3 high CD11b − CD27 − immature NK cells that were present only in TNBC samples. These tumor-infiltrating NK cells expressed a reduced cytotoxic granzyme signature and, in mice, were responsible for activating cancer stem cells through Wnt signaling. NK cell–mediated activation of these cancer stem cells subsequently enhanced tumor progression in mice, whereas depletion of NK cells or Wnt ligand secretion from NK cells by LGK-974 decreased tumor progression. In addition, NK cell depletion or inhibition of their function improved anti–programmed cell death ligand 1 (PD-L1) antibody or chemotherapy response in mice with TNBC. Furthermore, tumor samples from patients with TNBC and non-TNBC revealed that increased numbers of CD56 bright NK cells were present in TNBC tumors and were correlated to poor overall survival in patients with TNBC. Together, our findings identify a population of protumorigenic NK cells that may be exploited for both diagnostic and therapeutic strategies to improve outcomes for patients with TNBC.
Sensitive detection of single-nucleotide polymorphisms by conjugated polymers for personalized treatment of hypertension
Authors: Qi Shen, Honghong Zhang, Yiming Huang, Mingyu Li, Hao Zhao, Zhiwen Yang, Haijing Zhao, Qi Liu, Zihao Fu, Yufei Di, Libing Liu, Haotian Bai, Fengting Lv, Yundai Chen, Yuqi Liu, Shu Wang
Journal: Science Translational Medicine (2023)

Genetic variants among individuals have been associated with ineffective control of hypertension. Previous work has shown that hypertension has a polygenic nature, and interactions between these loci have been associated with variations in drug response. Rapid detection of multiple genetic loci with high sensitivity and specificity is needed for the effective implementation of personalized medicine for the treatment of hypertension. Here, we used a cationic conjugated polymer (CCP)-based multistep fluorescence resonance energy transfer (MS-FRET) technique to qualitatively analyze DNA genotypes associated with hypertension in the Chinese population. Assessment of 10 genetic loci using this technique successfully identified known hypertensive risk alleles in a retrospective study of whole-blood samples from 150 patients hospitalized with hypertension. We then applied our detection method in a prospective clinical trial of 100 patients with essential hypertension and found that personalized treatment of patients with hypertension based on results from the MS-FRET technique could effectively improve blood pressure control rate (94.0% versus 54.0%) and shorten the time duration to controlling blood pressure (4.06 ± 2.10 versus 5.82 ± 1.84 days) as compared with conventional treatment. These results suggest that CCP-based MS-FRET genetic variant detection may assist clinicians in rapid and accurate classification of risk in patients with hypertension and improve treatment outcomes.